Bone implants and method of manufacture

ABSTRACT

An implant device for humans or mammals has a body structure having an exposed surface and one or more selected portions of the exposed surface having a bone formation enhancing 3-dimensional pattern. The exposed surface can be on exterior portions of the body structure or internal portions of the body structure or both. The one or more selected portions of the exposed portions having the bone formation enhancing 3-dimensional patterns are in the external exposed surfaces or in the internal exposed surfaces or both internal and external exposed surfaces.

RELATED APPLICATIONS

This application is a divisional of U.S. Ser. No. 13/303,944 filed onNov. 23, 2011.

FIELD OF THE INVENTION

The present invention relates to bone implants, and more particularly toan improved implant and an improvement in the manufacture of suchimplants.

BACKGROUND OF THE INVENTION

The use of skeletal implants is common in surgical repairs. Implants areemployed in a variety of procedures such as spinal repair, knees, hipsor shoulders and others. A common and most important feature of manyimplants is the integration of the implant into the skeletal structure.Mechanical fasteners, sutures and adhesives and other ways of affixingthe device to the bone structure are used. These implants can befashioned from human bone or other biological material or alternativelycan be made from implantable grade synthetic plastics or metals likestainless steel, titanium or the alloys of metals suitable forimplantation.

One of the benefits of these plastic or metal implants is the strengthand structure can be specifically designed to be even more durable thanthe bone being replaced.

As mentioned, one concern is properly securing the implant in place andinsuring it cannot be dislodged or moved after repair. One of the bestsolutions to this issue is to allow the surrounding bone structure togrow around the implant and in some cases of hollow bone implants toallow new bone growth to occur not only around, but throughout theimplant as well to achieve interlocked connectivity.

This is not particularly easy in many of the metal implants or hardplastic implants. In fact, the surface structure of the implant materialis often adverse to bone formation. On some implant surfaces this may infact be a desirable characteristic, but in those procedures where newbone growth formation is desirable this is problematic.

It is therefore an object of the present invention to provide animproved implant device that encourages new bone growth formation atselected surfaces of the device. The selected surfaces can be some orall external or internal exposed surface features of the implant device.The device with exposed surfaces that have selected surfaces for bonegrowth formation can be prepared by the methods as described below.

SUMMARY OF THE INVENTION

An implant device for humans or mammals has a body structure having anexposed surface and one or more selected portions of the exposed surfacehaving a bone formation enhancing 3-dimensional pattern. The exposedsurface can be on exterior portions of the body structure or internalportions of the body structure or both. The one or more selectedportions of the exposed portions having the bone formation enhancing3-dimensional patterns are in the external exposed surfaces or in theinternal exposed surfaces or both internal and external exposedsurfaces.

The 3-dimensional pattern is made of a substantially continuous networkhaving voids or indentations. The voids or indentations have a mediumwidth of about 30-300 microns and at least 10 percent of said voids havea fractal dimension of at least 3 microns. The voids have a depth intothe selected surface of about 150 microns or less. In a preferredembodiment the 3-dimensional pattern mimics a marine or sea mammal bonestructure such as a whale or dolphin. The voids have a medium width of500-800 microns in the open marrow regions of the implant device whenformed as a trabecular bone structure.

The body structure is made of an implantable plastic or polymer or ismade of a metal suitable for implanting in a human or mammal. The metalcan be titanium or a titanium alloy or a stainless steel or a stainlesssteel alloy.

The body structure can be made of an implantable grade syntheticplastic, which is a thermoplastic or thermoset material. The plasticmaterial can be any implantable grade material such as PEEK (polyetherether ketone), PEKK (polyether ketone ketone), polyethylene, ultra highmolecular weight polyethylene, polyphenylsulfone, polysulfone,polythermide, acetal copolymer, polyester woven or solid or implantablegrade lennite UHME-PE. The implant device may include anchoring holes tosecure the device to the skeletal structure with fasteners oralternatively can simply be held in place by and between adjacentskeletal structures. The implant device can be built by additivefabrication through a process offering reproducible and reconcilableformation to the istropic domains inherent to the marine mammalcancellous bone. In such application, the internal structure is modeledfor strength, neutralized for strain, and open to surface modificationof its entire network of trabecular permutations.

DEFINITIONS

As used herein and in the claims:

“Exposed surface” means surfaces that are typically an outer or planarfeature of 2-dimensions as used herein and throughout this description.“Exposed surface” means an outer skin or surface having a depthproviding a 3-dimensional character, this depth being the distance thesurface pattern penetrates into the body structure of the device toproduce a repeatable pattern for enhancing bone formation on the implantdevice. The exposed surface might also include an open trabecularstructure wherein the voids extend from the surface throughout thestructure.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is described by way of example and with reference to theaccompanying drawings in which:

FIG. 1 shows a Type-I collagen matrix cut by free-electron laser toreproduce cancellous bone according to the state of the art.

FIGS. 1A-1K are a number of perspective views of exemplary synthetic,metallic or a combination thereof which can additionally include amicroceramic admixture with PEEK or PEKK or titanium implant devicesthat can be made according to the present invention.

FIG. 1A shows an implant device made according to the present invention.

FIG. 1B shows a first alternative embodiment made according to thepresent invention.

FIG. 1C shows a second alternative embodiment made according to thepresent invention.

FIG. 1D shows a third alternative embodiment made according to thepresent invention.

FIG. 1E shows a fourth alternative embodiment made according to thepresent invention.

FIG. 1F shows a fifth alternative embodiment made according to thepresent invention.

FIG. 1G shows a sixth alternative embodiment made according to thepresent invention.

FIG. 1H shows a seventh alternative embodiment made according to thepresent invention.

FIG. 1I shows an eighth alternative embodiment made according to thepresent invention.

FIG. 1J shows a ninth alternative embodiment made according to thepresent invention.

FIG. 1K shows a tenth alternative embodiment made according to thepresent invention.

FIG. 2 shows a collagen scaffold or sheet representing cancellous boneaccording to the invention, wherein a tile pattern has been used.

FIG. 2A is a photo reproduction of cancellous whale bone, the largeportion being of the same scale as shown in FIG. 2, the upper left viewbeing at scale, the lower left view being magnified.

FIGS. 3A and 3B shows two longitudinal sections of allograft fibermaterial after 3 and 6 weeks of culturing with cells according to thestate of the art. Differing in magnification, no apparent difference insize was evident despite the much thicker matrix that attached to theNDGA-treated fibrils.

FIG. 4 shows the fibroblast attachment to tissue-culture treated dishescoated with collagen, and collagen-coated dishes treated with NDGA. Thenumber of cells attached following removal of unattached cells withDulbecco's PBS measured with CyQuant cell proliferation assay.

FIG. 5 is a schematic representation of a laminate structured sheetmaterial having different (controlled) degradability.

FIG. 6 is a perspective view of one of the exemplary devices of FIG. 1Awith a pattern on the exposed surfaces and a wrapping of a sheet fromFIG. 2.

FIG. 7 is a perspective view of one of the exemplary devices of FIG. 1Awith a pattern on the exposed surface made according to the presentinvention.

FIG. 7A is a perspective view taken from FIG. 7 of the exemplary deviceof FIG. 1A wherein the device has been magnified in size to match thescale of the pattern of FIG. 2.

FIG. 8 shows a schematic drawing of a device for producing a sheetmaterial according to the present invention by rolling.

FIG. 9 shows another schematic drawing of the device according to FIG.8, further equipped for producing thin wafer material for producing asheet material laminate.

DETAILED DESCRIPTION OF THE INVENTION

Orthopaedic surgeons have been applying the principles of tissueengineering for years, transplanting and shifting matrices withinpatients to promote regenerative potential. The advent of new technologyoffers even greater promise and brings unbridled enthusiasm that fullregenerative potential of tissue and whole organ systems can be achievedin the near future. While soft tissue repair can be managed by achievingscar tissue replacement, such outcome in most orthopaedic applicationsand indications would be insufficient. Bone requires tissue-specificcomposition attendant to its function for skeletal support. Formation ofcollagenous material alone, even if vascularized, will fail to meet thebiophysical demands of repetitive skeletal loading and be inadequate.

Implicit in the goals of repairing bone are to achieve restitution ofspace, mechanical solidarity, and functional continuity. Often thebiological signals do not provide sufficient stimulus to attain a fullrepair. Orthopedic interventions to alleviate fracture nonunion,pseudarthrosis, and scoliosis; bone defects due to congenital ordevelopmental anomalies, infection, malignancy, or trauma often requirebone grafting to augment the process of bone healing. The therapeuticgoal of graft material is to omit compliance features such as straintolerance, reduced stiffness, and attenuated strength, and insteadpromote primary, or membranous-type bone formation within the physicalapproximation of a graft material. Three basic components are required:osteoprogenitor cells, osteoinductive factors, and an osteoconductivematrix or scaffold.

Autologous cancellous bone remains to date the most effective graftmaterial, where osteoinductivity, osteoconductivity, and a rich sourceof cells endow the material with not only biological activity but adegree of immunologic transparency as well. Because of complications andshortcomings associated with autogenous grafting that include limitedquantity, donor-site morbidity, and more recently cost consideration(1), numerous alternative graft materials have been developed fororthopedic applications.

Available grafting substitutes include cancellous and cortical allograftbone, ceramics such as sintered coralline matrices, hydroxyapatite andtri-calcium phosphate, demineralized bone matrix, bone marrow, compositepolymer grafts, and recently recombinant cytokines with collagencarriers. Complications include availability, cost, variablebioabsorption, brittleness, immune stimulation, and regulatory hurdles.

Future bio-engineering strategies will combine several favorableproperties of the current items in an effort to achieve hybrid materialsthat support tissue differentiation without shielding capacity forintegrated modeling. Ideally, new materials will provide tissuecompatibility and minimize patient morbidity. The goal of this inventionis to provide an implant that will be not only structurally enhancingbut inductively optimum for bone formation. Relying on a defined patternto promote conductivity, this manufactured implant has been designed tostimulate cell differentiation and bone regeneration, and be utilized asan orthotopic alternative to tissue transplantation.

The concept for manufactured implant depends on a capacity to achievereproducible design in a geometric pattern on an exposed surface of theimplant. Such implants will support osteoblast attachment and permitbone-specific matrix production. In light of anticipated rulings by theFDA for greater control of tissue products for transplantation,developing alternative materials with comparable osteoinductivity seemsappropriate. Several features combine to make this proposal unique;first, the bone model for the architecture approximates an under-modeledmammal, using increased porosity to accelerate ingrowth; second, aunique cross-linking methodology reduces the bioabsorption rate of humancollagen and effects a mechanically competent selected surface; andthird, osteoblasts can be used to deposit a bone matrix onto the devicethat will make it osteoinductive. The controlled process is intended totake advantage of previous regulatory considerations of human collagenas a device. FDA approval for human collagen in combination withexcipient material is not unprecedented.

The shape of the geometric pattern template is critical to the successof manufacturing. A central tenet of biomineralization is thatnucleation, growth, morphology and aggregation of the inorganic crystalsof bone are regulated by organized assemblies of organic macromolecules.The close spatial relationship of hydroxyapatite crystals with Type Icollagen fibrils in the early stage of bone mineralization is a relevantexample. It is equally evident that combining hydroxyapatite withprotein does not render the macroscopic form of bone nor impart itscharacteristic properties. Unlike fabricated materials that can bedeveloped from components with predictable properties, biologicalsystems control desired properties by utilizing an intrinsic rationalethat discriminates essential from non-essential factors. Livingorganisms avoid the geometric frustration of randomness by segregatingstructure that resonate function.

Although bone can appear de novo, it more often develops from accretionon a scaffold of matrix that contains appropriate vascular andcompositional arrangement. As such, 3-dimensional patterns enhanceosteoconductivity. Bone has significantly more matrix than cells, andcell regulation through anchorage dependent mechanisms is an establishedpremise. Compensatory mechanisms for changing sensitivity to mechanicalstimulation have been shown to undergo adaptive or kinetic regulation,likely tied directly to osteoblast attachment to immobilized moleculesin the extracellular matrix (ECM). ECM molecules promote cell spreadingby resisting cell tension, thereby promoting structural rearrangementswithin the cytoskeleton. Several lines of evidence suggest that tensionor mechanical stretch exerts a direct positive effect on bone cells andbone cell differentiation through: 1.) activation of phospholipase A2,2.) release of arachidonic acid; 3.) increased prostaglandin Esynthesis; 4.) augmented cyclic adenosine monophosphate (cAMP)production; and 5.) and expression of the bone-associated transcriptionfactor CBFA-1. It has long been recognized that a sustained increase inthe cellular level of cAMP constitutes a growth-promoting signal, andthat prostaglandins directly effect a change in cell shape and increaseintercellular gap junctions. Without a capacity for attachment andspreading, cells undergo apoptosis, or programmed cell death.

Bone withstands compressive loading by efficient distribution ofinternal tensile forces. Bone cells do however adhere to structures thatcan resist compression in order to spread, engaging osteoblastattachment, mineralization, and bone matrix organization as linkedprocesses. Even though deformation at the tissue level might beevaluated as an ability to resist compression, force along individualtrabeculae reflects an ordinate of new tension. Under normal cycles ofdevelopment, increased mass conveys a progressive stimulus of tension tocells, gravity imposing a unidirectional vector to terrestrial life.

A sudden reduction in gravity imposes serious consequence to theskeleton. As shown by studies of astronauts, marked skeletal changes inthe weight-bearing skeleton including a reduction in both cortical andtrabecular bone formation, alteration in mineralization patterns, anddisorganization of collagen and non-collagenous protein metabolism havebeen associated with microgravity. Each month of spaceflight results ina 1-2% reduction of bone mineral density that has been linked todown-regulated PTH (parathyroid hormone) and 1, 25-dihydroxyvitamin D3production. Indices from cosmonauts aboard Euromir 95 account boneatrophy to both a reduction in bone formation and increased resorption.PTH decreased (48%), as did bone alkaline phosphatase, osteocalcin, andtype-I collagen propeptide. At the same time bound and freedeoxypyridinoline and pro-collagen telopeptide increased. The chords ofinformation establish a role for microgravity in uncoupling boneformation and enhancing resorption.

If exposure to microgravity demonstrates physiologic responses thatmirror a reduction in trabecular tension, then would reciprocity offunction be expected in bone that is modeled under microgravity and thenexposed to normal gravitational force? Prolonged weightlessness, asexperienced in space flight, effectively unloads the skeleton, relaxingtension on the trabeculae. In this manner, osteoblast physiology will bealtered due to attachment perturbations. Conversely, a bioscaffoldmodeled in the form of tissue that has developed under microgravity,will experience an enhanced tensile loading sensation on individualtrabeculae. This has the inventor of the present invention to predictthat cells attached to this matrix will undergo a direct stimulus, anddisplay enhanced osteoblast physiology as demonstrated in themechanotransduction studies previously noted.

It is this invention's intent to duplicate the architecture ofunder-modeled cancellous bone, guided by the idea that a material laterpopulated with bone cells will more quickly respond to the mechanicaland biological roles of bone with subsequent loading. Because cancellousbone is a porous structure, its mechanical properties are dependent uponthe distribution and arrangement of its structural elements, ortrabeculae. Considering three-dimensional architecture to be critical tothe mechanical integrity of trabecular bone, his work established themorphometry of under loaded marine mammal tissue. The rationale for thisapproach is based on the observation that pre-natal cancellous bone inhumans has unique potential for rapid post-natal modeling, and thatcell-culture studies performed during orbital space flight demonstratesignificant osteoblast stimulation upon return to increasedgravitational field. In the case of sea mammals, separate environmentbuoyancy suppresses loading variation, resulting in minimal secondarybone formation and modeling. Whale bone retains a primary trabecularstructure and does not remodel according to standard parameters ofmechanical adaptation. Trabecular morphology and osteocyte number aresimilar among commonly oriented blocks, while significant differencescan be demonstrated between tissue sections studied in planesperpendicular to the axial length of bones (Table 1).

TABLE 1 BIOPSY BV/TV BS/BV TbTh TbSp TbN Ost # Cross 17.71 14.98 135.16631.70 1.33 230/mm² Long 24.54 8.67 231.05 710.98 1.06 150/mm²BV/TV—Bone Volume/Tissue Volume; BS/BV—Bone Surface/Bone Volume;TbTh—Trabecular Thickness = μm; TbN—Trabecular Number; Ost #—osteocytecells per mm2.

Bone examined in longitudinal dimension demonstrated greater trabecularseparation, thicker trabeculae, yet because of the lesser number oftrabecula, still structured less bone surface per volume of tissue.Although bone surface to bone volume, trabecular thickness, andtrabecular number followed predicted allometric extrapolation, bonevolume was considerably less than that scaled for land mammals, and wasreflected in greater trabecular separation and reduced trabecularnumber. It is this separation and thickness that provides a basis forbio-reactor cell culture and offer the chance to manufacture bone.

To best take advantage of the improved implant device of the presentinvention, it is believed that the selected 3-dimensional pattern can beapplied on all or parts of the exposed interior or exterior surfacesassuming the method of preparing the surface permits, and thattechnology is also available to define a structural solid incorporatingthe porosity without reducing the loading capacity in the context oftensile stiffness.

For example, if an embossing technique is used wherein the pattern ispressed into the selected surfaces of the implant device then it isapplied on suitable exposed exterior surfaces. Similarly if the methodof etching or engraving is used, the exterior surfaces can be easilyprepared and some, but not necessarily all exposed internal surfaces canhave a portion covered by the 3-dimensional pattern.

As shown in FIG. 2, these 3-dimensional patterns 100A are mostconveniently applied to thin layers 10A which can be collagen basedlayers 10A as disclosed in co-pending U.S. patent application Ser. No.13/303,811 (attorney docket number 0191) entitled “Bone Graft” filed onNov. 23, 2011 concurrently with the present application which isincorporated by reference herein in its entirety. These thin implantlayers 10A provide a maximum surface substantially planar exposedsurface which can effectively achieve a 3-dimensional pattern 100A onone or both of the top or bottom surfaces a patterned sheet structure ofscaffold 2. These layers 10A can be assembled to form 3-dimensionalscaffolds which can form the body structure in part or all of animplant.

As shown in FIG. 2, the sheet 2 with a pattern 100A is shown magnifiedat least 5 times to enable the 3-dimensional pattern to be more readilyvisible. The pattern as illustrated is proportionally accurateotherwise. With reference to FIG. 2A is a photo reproduction ofcancellous whale bone, the large portion being of the same scale asshown in FIG. 2, the upper left view being at scale, the lower left viewbeing magnified. This actual pattern 100W of whale bone closelyresembles the reproduced 3-dimensional pattern 100A and clearly mimicsthis whale bone structure.

To better illustrate the pattern 100A, each device 10 is shown with the3-dimensional pattern 100A illustrated as a magnified portion separatein a magnified circle and a reference line pointing to the exposedsurface. It is understood this pattern 100A is very small and in orderto visualize its appearance, this circle of the magnified surface 13depicting the pattern 100A is provided. To try and illustrate thepattern 100A at true scale would result in the appearance of sandpaperof a fine grit similar to the skin of a shark. For this reason, thepattern 100A is shown separate and magnified, when in practice, thedevice 10 actually can have the entire exposed surface covered by thepattern 100A. The 3-dimensional pattern 100A is made of a substantiallycontinuous network having voids or indentations. The voids orindentations have a medium width of about 30-300 microns and at least 10percent of said voids have a fractal dimension of at least 3 microns.The voids have a depth into the selected surface of about 150 microns orless. In a preferred embodiment the 3-dimensional pattern mimics amarine or sea mammal bone structure such as a whale or dolphin. Thevoids have a medium width of 500-800 microns in the open marrow regionsof the implant device when formed as a trabecular bone structure.

In certain devices the layers 10A can be made of implantable gradeplastics or metals which are assembled together in a laminate sheetstructure 2 having the selected 3-dimensional pattern 100A on thesurfaces of adjacent layers 10A. This is believed an ideal way toachieve enhanced new bone growth in the region of the implant as shownin FIG. 5.

Alternatively, the improved implant device 10 can be a molded, machinedor otherwise manufactured 3-dimensional device having a specific bodystructure 12 with exposed surfaces 13 onto which the repeatablegeometric 3-dimensional pattern 100A can be placed on selected portionsof the exposed surface to create a continuous network of voids whichwill enhance bone formation, as shown in FIG. 7. With reference to FIG.7A, the device 10 has been magnified in size such that the 3-dimensionalpattern 100A is of the same scale as shown in FIG. 2 allowing for abetter view of how the pattern is applied to the exposed surfaces 13.Exposed surfaces can be defined and developed throughout the implantbased on manufacturing technique, for example, if the implant is made asan assembly of layers, the pattern can extend throughout the bodystructure of the device. Furthermore, addictive fabrication technologywith thermoplastic lasering might also be used to attest a shape fromthe molecular components of powdered ingredients.

It is most beneficial if the repeatable 3-dimensional geometric patterncan be achieved as part of the initial manufacture of the implant device10 by imparting a negative onto the molding surfaces or in a cast of asintered metal part. It must be appreciated that the size of the voidsbetween the ridges 103 and channels 101 of the pattern 100A shown in thesheets 2 of FIG. 2 are extremely small and as a result such patternformation to be repeatable in the surfaces 13 can be assured by asecondary procedure of embossing, etching, micropatterning or pressingonto an exposed surface 13 of the implant device 10. Chemical etching,while feasible, can be used with the understanding the implant 10 mustbe free if any residual chemical that could be adverse to boneformation. Plasma deposition can also be used to form the pattern on theexposed surfaces of the device. Plasma-enhanced chemical vapordeposition (PECVD) is a process used to deposit thin films from a gasstate (vapor) to a solid state on a substrate.

Most importantly, in the preferred embodiment, the geometric3-dimensional pattern 100A is selected to duplicate or at least closelymimic the pattern of a marine mammal such as a whale. While this pattern100A is preferred, other similar patterns that approach the voidpercentage depth and shape of a human pre-natal cellular structure arealso considered optimal alternatives. The main distinction of thissurface pattern 100A is that it is repeatable. Conventional surfacetreatments that roughen a surface to improve chemical adhesion simply donot achieve this ability to enhance bone formation about an implantdevice. Whereas this repeatable pattern 100A has demonstrated thisability. Ideally, the implant device 10, once prepared with a suitable3-dimensional pattern 100A, can be used in the surgical procedure forwhich it was designed without any alteration in the procedure withconfidence that the prepared pattern surfaces 100A will facilitate newbone formation. Alterntiavely, more preferably, these improved implantdevices 10 can be also treated with gels or coatings or sheets ladenwith bone formation enhancing cells which will find the patternedsurfaces ideal for growth and adherence. Alternatively, the geometric3-dimensional pattern 100A is selected to duplicate or at least closelymimic the pattern of a marine mammal such as a dolphin.

Once the geometric 3-dimensional pattern 100A is achieved in areproducible manner on a selected surface of an implant device 10, itcan be coated or otherwise treated with cells to enhance bone creationand bone formation in the selected areas of the pattern oralternatively, the implant device 10 can be simply implanted relying onthe patient's tissue to attach and initiate bone formation de nova.

One interesting opportunity in the use of 3-dimensional patterns 100A isto produce a negative pattern and a positive pattern on adjacentstructures. For example, a scaffold or sheet 2 as described in the abovereferenced co-pending application can have a negative pattern and theimplant device 10 can have a positive pattern in a selected exposedsurface 13. The two can be assembled into an abutting relation bywrapping the sheet 2 onto the device 10 to cause the mating surfaces toenhance bone formation as illustrated in FIG. 6.

It is important to appreciate the improved device provides a beneficialsurface to facilitate bone creation more quickly than in the absence ofthe 3-dimensional patterns. Furthermore, unlike a surface texture orroughening to enhance chemical bonding, the selected geometric patternsmimic pre-natal cancellous bone formation, which ideally, stimulates abiological response not otherwise appreciated or achieved in syntheticor metallic structures. The most common implants are load bearingdevices with direction forces imparted due to the molding process.Isotropic structures are not bound in design by a vector of directionalforce. A biomaterial with no loading history supports integration thatis singularly directed and substantially more efficient because it comesfrom a neutral state of loading, the forces guiding the new bone arebiologically consistent with not the history of the materialconstruction, but the combined geometry of the implant plus theregenerative potential of the construct. In instance, the intention ofusing the whale bone as a foundation material is that it has the samemechanical properties regardless of the direction of loading. Thisisotropy is a fundamental value to an inert prosthesis as it does notshield in any way the active loading signals during the fusion, orregenerative process. The integration is through the unit, not aroundthe unit. As the PEEK material is inert, any preset conditions for itsstructure must be overcome and neutralized before material properties ofthe regenerative repair can be focused. The use of the pattern 100Amimics the whale bone and neutralizes these flow stresses in the exposedsurface of the body structure 12 of the molded type such as PEEK device10.

The use of an implant device similar to that illustrated in FIGS. 1A, 6and 7 shows a very open or exposed device which affords numerous exposedsurfaces 13 as selected areas for applying the 3-dimensional pattern.The device 10 itself being open affords improved opportunity for boneformation internally and externally and therefore is highlycomplimentary to the concepts of pattern formation to enhance bonegrowth.

For purposes of the present invention, any device suitable forimplanting having an exposed surface 13 onto which a bone formationenhancing pattern 100A is considered within the scope of the presentinvention, these include any skeletal implant including spine, hips,knees, shoulders, neck, feet, hands or any bone like repair implant. Theshape of the body structure can be any shape where an exposed internalor external surface is available to apply 3-dimensional bone growthenhancing patterns. The implant device can be of any shape includingspheres, hemispheres, ovals, disks, rings, rectangles, squares, solid orhollow tubes or the like.

With reference to FIGS. 1A-1K, a number of perspective views ofexemplary synthetic metallic or combinations thereof of some typicalimplants 10 that are made according to the present invention areillustrated. Each of the implants 10 as shown has a metallic, syntheticor combination of metallic and synthetic implant body structures 12. Theimplant body structures 12 as shown are designed for insertion on orinto a skeletal spinal structure of a patient. FIG. 1A is the PhenixCID, FIG. 1B is the Talos-P PLIF, FIG. 1C is the TLIF, FIG. 1D isTalos-T TLIF, FIG. 1E is entitled OLIF, FIG. 1F is Talos-A ALIF, FIG. 1Gis LLIF, FIG. 1H is Thor Standalone ALIF, FIG. 1I is the DiamondCervical Plate, FIG. 1J is the Facet Screw Skirt and FIG. 1K is asynthetic woven pouch used in bone grafting and repair. These devicesare simply examples and not intended to be limiting in any way.

Each of these exemplary spinal implant device examples are manufacturedand sold by Amendia or are competitor's alternatives that are alsoavailable for this purpose. For the purposes of simplification, each ofthese devices are commonly referred to by reference numeral 10 for thedevice and 12 for its body structure even though they are structurallynot the same in appearance each device 10 shown in FIGS. 1A-1K isdesigned to function as a spinal implant device made in accordance tothe present invention.

With reference to FIG. 1A, the Phenix CID, Phenix·—Cervical InterbodyDevice: Is a rectangular implant comprised of PEEK-OPTIMA® polymer fromInvibio Biomaterial Solutions, a radiolucent material with propertiesthat match the modulus of elasticity of cortical bone. The Phenix™ isintended for use with supplemental spinal fixation systems that havebeen labeled for use in the cervical spine. The Phenix “PEEK-OPTIMA®polymer from Invibio Biomaterial Solutions Cervical Interbody Device isavailable in a range of sizes and heights to fit any anatomy andincludes heights up to 12 mm. Available sizes range from a traditional12 mm×12 mm implant for small vertebral bodies to a 17 mm wide×14 mm A/Pimplant that sits at the load bearing perimeter of the vertebral bodyand contains a large graft window.

With reference to FIG. 1B, the Talos-P PLIF, the Talos®-P is aPEEK-OPTIMA lumbar interbody device for PLIF approach. This cage isavailable in 3 lengths, 2 widths and a complete range of heights withinstrumentation that combines with the Talos®-T in one set to provide acomplete Posterior and Transforaminal solution.

With reference to FIG. 1D, the Talos-T TLIF, The Talos®-T is aPEEK-OPTIMA lumbar interbody device for TLIF approach. The Talos-T is acurved cage with a functional system for guiding the implant to a properposition. The instrumentation of the Talos®-T is combined with theTalos®-P instrument set to provide a flexible solution for Posterior andTransforaminal approaches. It includes angled teeth to prevent implantmigration, tapered nose aids in insertion and distraction, angled shapeimproves fit between vertebral bodies, functional tamps to guide implantto proper position and tantalum markers.

With reference to FIG. 1E, the Talos-O OLIF, the Talos®-O is a trulyunique percutaneous PEEK-OPTIMA lumbar interbody device that isdelivered through an oblique approach. This interbody is deliveredthrough an annular incision that is anterior to the transverse process,and is totally percutaneous. The PEEK-OPTIMA implant distracts andprovides unquestioned rigid anterior support for the vertebral body.This oblique approach is achieved for all lumbar segments, including theL5-S1 disc space. Our discectomy instruments work through the smallaccess portal to provide a complete percutaneous discectomy. Implantsare available in lengths and heights to accommodate all varieties oflumbar interbody spaces. Features include percutaneous delivery,distraction, intervertebral space, anatomical design for implantation,instrumentation for percutaneous discectomy, tapered shape glides pastthe nerve root, cannulated delivery that preserves safe pathway to thedisc space, angled teeth to prevent implant migration and tantalummarkers.

With reference to FIG. 1F, the Talos-A ALIF, the Talos®-A is atraditional ALIF interbody device that is available in a range of sizesto accommodate every anatomic requirement. Instrumentation is providedfor delivery from an Anterior or Anterolateral approach. A variety oflordotic angles and sizes are available. It includes chamfered cornersprovide anatomical fit, angled teeth prevent implant migration, twoinsertion options for anterior or anterolateral approaches, lordoticangles to match spinal anatomy, implant trials and rasps for preparingdisc space and tantalum markers.

With reference to FIG. 1I, the Diamond Cervical Plate, the DiamondAnterior Cervical Plate is a world class cervical plating systemutilizing a unique self-locking mechanism that is effortless to engageand offers superior screw retention while providing a simple revisiontechnique. The Diamond Cervical Plate is offered in single through fourlevel varieties and has the option of fixed or variable screws, andself-tapping or self-drilling. Rescue screws are also provided. Benefitsinclude; superior back-out resistance, fixed and variable screws forrigid, dynamic, or hybrid stabilization, variable screws allow 30degrees of freedom, low profile, easy to revise, color-coding of screwsfor length and fixed/variable head identification, instrumentationdesigned to reduce surgical steps, diamond window allows for greatergraft visualization and self-drilling tip or conservative self-tappingtip.

FIG. 1K shows a surgical mesh made of a Polyethylene Terephthalate (PET)mesh pouch designed to contain impacted granular bone graft and enableits incorporation. The mesh is used most commonly for traumatic fracturerepair and interbody fusion.

As shown in FIGS. 1A through 1H, each of the body structures 12 isprovided with at least one vertically oriented channel 16 or aperturewhich extends through the implant device 10. These channels 16 areprovided to enable bone tissue or bone graft material to be insertedinto the device during a surgical procedure. Some of the exemplaryembodiments have a lateral or side opening or channel 18. The sideopenings or channels 18 are provided to enable an x-ray to pass throughthe implant device in order to establish bone formation in the patientafter surgery has been completed and the implant has been inserted for aperiod of time. Additionally, some implants 10 may have holes 15 such asin the diamond cervical plate 10 of FIG. 1I threaded or otherwise toallow the device 10 to be secured or anchored to the spinal skeletonstructure between adjacent vertebrae if so desired. Several of thedevices are shown with jagged or toothed outer surface 17 on the uppersurface 11 and lower surface 13, these features help the device 10 toengage the vertebrae when implanted and help hold the device 10 intoposition between adjacent vertebrae during the surgical procedure. Theexterior surface of the body structures 12 of each of these devices canbe coated with a coating 22 gel or spray of a biological substance ormaterial containing stem cells 21 when made according to the presentinvention.

Alternatively, as illustrated in FIG. 2, a sheet 2 of material can beprovided that has the pattern 100A on a collagen layer 10A. This sheet 2can be wrapped around each of the exemplary implant devices 10 at thetime of surgery if so desired. This is illustrated in FIG. 6.Alternatively, as will be discussed later the sheet 2 can form a wraparound the implant device 10 which can be pre-assembled at amanufacturing facility in a sterile environment, packaged and shipped tothe medical facility for direct use as a surgical implant with a sheet 2material wrapped about the outer surface of the implant device 10. It isthis combination of the implant device 10 with a sheet of material 2that provides an enhanced ability of the implant to be accepted by thepatient in order for the implant to be fused by enhanced bone growthbetween vertebrae if so desired. Ideally as previously discussed, theimplant device 10 also has the pattern 100A on the exposed surface 13wrapped by the sheet 2. This combination provides a large bone growthenhancing surface between the device 10 and the sheet 2 to promote bonegrowth.

Typically the channels 101 having exposed surfaces with the pattern 100Aof the implant devices 10 can be filled with bone graft material eitherin a paste form or in solid bone material. This material during thepatient's healing is expected to fuse with the adjacent vertebrae and byproviding an envelope or covering so that the implant device 10 will bemore quickly fused to the spinal skeletal structure in a faster morerapid fashion due to the ability of the cells to trigger theregenerative process and to allow the adjacent bone structure to growaround the implant device more quickly than would occur otherwise in theabsence of the material 2.

Advancements in technology and refinements in application now permitreproducible templates of geometric patterns to be made with 10-micronresolution. Based on high resolution micro-CT analysis of blocks ofwhale bone (Microphotonics, Inc., Allentown, Pa.) surface material cannow be reproducibly made that replicate the cancellous morphology ofunder-modeled mammalian bone (FIG. 2) using template driven masking(Intelligent Micropatterning, LLC, St. Petersburg, Fla.). Advancementsin technology and refinements in application now permit reproducibletemplates 100A of collagen to be made with 10-micron resolution. Basedon high resolution micro-CT analysis of blocks of whale bone(Microphotonics, Inc., Allentown, Pa.), and Micro-CT Center, UCONNHealth Center), planar stacks of material 10 can now be reproduciblymade that replicate the cancellous morphology of under-modelledmammalian bone, as shown in FIG. 2, using template 100A drivencompression molding derived from patterns 100A detailed (IntelligentMicropatterning, LLC, St. Petersburg, Fla.) and etchings defined inmetal masters rollers 44, 46 (Akron Metal Etching, Co., Akron, Ohio) asshown in FIGS. 8 and 9 material 40 can be achieved repeatedly in sheetsor layers 2. Among the recently developed scaffolds for tissueengineering, polymeric hydrogels have proven satisfactory in cartilageand bone repair and can be used in combination with the present implantdevice. Peptide self-assembly has been shown to be a useful tool for thepreparation of bioactive nanostructures, and recent work hasdemonstrated their potential as therapies for regenerative medicine andthis technology can be applied to the present invention as well. Usingamphiphilic molecular domains, either as primary links, or byincorporating known enzymatic cleavage strategies, it is possible toaccentuate surface charge potential and thereby heighten the response toregenerative challenge.

Table 2 is the morphometric data of human cancellous bone samples H-1-H4and whale cancellous bone W1. Briefly the entire specimen was imaged andthe whale bone was purposely cut large to look for the internalconsistency of the form to follow variation in scales of sizing. Thecancellous bone samples range from 1-4 also in order of being mostosteoporotic (1) and the number (4) specimen being the most normal bone.Number 3 specimen is likely an outlier and might sit adjacent to acortical margin. The whale bone is consistent independent of boundaryrange or isometric randomization to size. The value in the whale bone isto isotropic distribution, thicker trabecula, greater trabecularspacing, and highest tissue density with lowest connectivity forequalized total volume. The importance is ridge dynamics, higher densitywith lesser void despite having greater separation makes this an idealpattern for mimicking to enhance new bone growth in humans.

TABLE 2 Trab Trab Bone Sam-

Thick- Trab Spac- Connec Apparent Tissue Total Bone Sur- BS/ BS/ BS/ ple

ness Number ing Density Density Density Volume Volume face BV TV MV No.

DA Just within boundaries of pieces H1 14.0% 142 1.41

570.999

1.7

2.

3.3 1.6 H2 21.0% 146 1.69 521  7 149

541.047 113.

0.

17.2 3.7 4.7 2.8 H3 24.0% 191 1.

1

17 417.510 100.

1.0 1

13.

3.4 4.4

H4

156 2.24 374 17 2

6 891

.271 120.

0.

1

6.0 7.3 1.7 Wt 21.1% 1

1.2

00

190 866 1070.286 225.320 0.4 3125.0

2.9 3.7 1.4 Smaller isometric cube

H1

%

1.6

 67

70.113 11.152 1.9

3.0 3.5 1.

H2 24.0% 160 1.

488

70.113

0.8 277.5 16.4 4.0 5.2

H3

% 174 1.7

4

218

70.113 18.451 0.9 266.0 14.4 3.6

1.7 H4 24.0%

2.36 3

18 319

70.113 24.256 0.0 372.6

5.3

1.7 Wt

.1% 167 1.29 7

 3 226

14.7

0.

212.9 14.3 3.0

1.5 Smallest isometric cube

H1 16.6%

1.

 94

45.084

1.8

3.0

1.6 H2 24.9%

1.

471

194

45.084 11.2

0.8

16.1 4.0

H3

1

1.

475  7 221 90

45.084 11.993 0.9 172.6 14.4 3.8 5.2 1.

H4

1

2.41 3

19

45.084 11.

0.1 243.7 15.2 5.4 5.4 1.7 Wt

1

1.32 754

220 902 45.084 9.17

0.4 134.6 14.6

3.7 1.5

indicates data missing or illegible when filed

Variations in the present invention are possible in light of thedescription of it provided herein. While certain representativeembodiments and details have been shown for the purpose of illustratingthe subject invention, it will be apparent to those skilled in this artthat various changes and modifications can be made therein withoutdeparting from the scope of the subject invention. It is, therefore, tobe understood that changes can be made in the particular embodimentsdescribed, which will be within the full intended scope of the inventionas defined by the following appended claims.

What is claimed is:
 1. The method of producing a bone implant having anexposed surface with one or more portions of the exposed surface havinga bone formation enhancing 3-dimensional pattern, the pattern comprisesthe step of creating the repeating pattern by one of molding, etching,embossing, machining, masking the pattern into select portions of theexposed surfaces.